The Paediatric Neurosciences Research Group, Royal Hospital for Children, Queen Elizabeth University Hospitals, Glasgow, UK; School of Medicine, University of Glasgow, Glasgow, UK.
The Paediatric Neurosciences Research Group, Royal Hospital for Children, Queen Elizabeth University Hospitals, Glasgow, UK; School of Medicine, University of Glasgow, Glasgow, UK.
Neuropharmacology. 2018 Apr;132:3-19. doi: 10.1016/j.neuropharm.2017.10.013. Epub 2017 Oct 14.
The genetic channelopathies are a broad collection of diseases. Many ion channel genes demonstrate wide phenotypic pleiotropy, but nonetheless concerted efforts have been made to characterise genotype-phenotype relationships. In this review we give an overview of the factors that influence genotype-phenotype relationships across this group of diseases as a whole, using specific individual channelopathies as examples. We suggest reasons for the limitations observed in these relationships. We discuss the role of ion channel variation in polygenic disease and highlight research that has contributed to unravelling the complex aetiological nature of these conditions. We focus specifically on the quest for modifying genes in inherited channelopathies, using the voltage-gated sodium channels as an example. Epilepsy related to genetic channelopathy is one area in which precision medicine is showing promise. We will discuss the successes and limitations of precision medicine in these conditions. This article is part of the Special Issue entitled 'Channelopathies.'
遗传性通道病是一大类疾病。许多离子通道基因表现出广泛的表型多效性，但人们仍齐心协力地描述基因型-表型关系。在这篇综述中，我们将以特定的单个通道病作为例子，概述影响整个疾病组基因型-表型关系的因素。我们提出了这些关系中观察到的局限性的原因。我们讨论了离子通道变异在多基因疾病中的作用，并强调了有助于揭示这些疾病复杂病因性质的研究。我们特别关注在遗传性通道病中寻找修饰基因的问题，以电压门控钠离子通道为例。与遗传通道病相关的癫痫是精准医疗显示出前景的一个领域。我们将讨论精准医疗在这些疾病中的成功和局限性。本文是主题为“通道病”的特刊的一部分。
